HIGH RISK DRUGS Flashcards
(105 cards)
1
Q
What is steady state?
A
4 or 5 half-lives after initiation of therapy or a change in dosage.
2
Q
What is a loading dose?
A
Higher initial dose to rapidly achieve therapeutic response. Drugs with long half-lives will take longer to reach steady state, therefore require a loading dose to rapidly achieve target concentration for acute therapeutic response
3
Q
What is the half life of Amiodarone?
A
LONG - about 50 days. Loading dose may be required
4
Q
What monitoring is needed for amiodarone?
A
Thyroid function, liver function, serum K, chest xray, ECG (with IV use)
5
Q
What is the indication for amiodarone?
A
- Treatment of arrythmias, particularly when other drugs are ineffective or c/i (including paroxysmal supaventricular, nodal and ventricular tachycardias, AF and flutter, ventricular fibrillation associated with Wolff-Parkinson-White syndrome)
6
Q
Warning signs for amiodarone?
A
- signs and symptoms of hypo/hyperthyroidism
- impaired vision (optic neuritis/neuropathy)
- photophobia, dazzled by headlights at night (corneal micro deposits)
- progressive s.o.b or cough (pneumonitis, pulmonary toxicity)
- clinical signs of liver disease e.g. jaundice
- neurological effects of tremor, peripheral neuropathy (e.g. develop numbness and tingling in hands and feet)
- phototoxic skin reactions e.g. burning sensation followed by erythema and persistent slate grey skin discolouration on light-exposed areas
7
Q
Action required when warning signs for amiodarone present?
A
- advise patient to shield skin from direct sunlight and for several months after stopping treatment or to use wide spec spf
- warn drivers that they may be dazzled by headlights at night
- warn patients that clinical effects may occur up to a year after stopping the medicine
8
Q
Amiodarone interations?
A
Due to long half life, there is potential for drug interations to occur for several weeks to months after treatment stopped.
- Increased plasma conc of coumarins (warfarin), dabigatran, digoxin, flecainide, phenindione, phenytoin
- Increased risk of ventricular arrhythmias when given with amisulpride, atomoxetine, chloroquine, citalopram, disopyramide, excitalopram, haloperidol. hydroxychloroquine, levofloxacin, lithium, mizolastine, mefloquine, moxifloxacin, phenothiazines, pimozide, quinine, sulpiride, telithomycin, tolterodine, tricyclics
- Increased risk of bradycardia, AV block and myocardial depression when given with BBs, diltiazem, verapamil
- Increased risk of myopathy when given with simvastatin
9
Q
What monitoring is needed for antihypertensives?
A
- Blood pressure
- heart rate
- renal function
- serum electrolytes
10
Q
What are the warning signs for antihypertensives?
A
- water retention
- heaviness in the centre of chest triggered by effort or emotion
- depression
- extreme tiredness, thirst or excessive urination
- irregular heartbeat, muscle weakness, nausea
- pain or tightness in legs while exercising that dissapears at rest
- dizziness, light-headedness on standing, blurred vision (postural hypotension)
11
Q
Action required when antihypertensive warning signs are present:?
A
- advise patient to report immediately to doctor
- advise patient to sit up and stand slowly first thing in the morning to prevent postural hypotension
- If dizziness experienced, avoid driving/operating machinery
- drink adequate (not excessive) volumes of fluids each day
- inform of potential interactions and check with pharmacist/doctor before taking any other new medication (incl OTC)
- advise patient on avoiding soluble OTC preparations e.g. analgesics due to high sodium content
- ensure the patient recieves the same brand of diltiazem or nifedipine MR prep each time
12
Q
Antihypertensive interations?
A
- Diltiazem, verapamil, amlodipine, ranolazine and high dose statins can increased risk of myopathy. Recommended max daily dose of simvastatin 20mg with concomitant diltiazem, verapamil, amlodipine or ranolazine.
- Increased plasma conc of ivabradine, aliskerin CCBs when given with grapefruit juice
13
Q
Carbamazepine indications?
A
- Epilepsy (focal and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic)
- Trigeminal neuralgia
- prohylaxis of bipolar unresponsive to lithium
- adjunct in acute alcohol withdrawal
- ## diabetic neuropathy
14
Q
What is the therapeutic range of carbamazepine?
A
4-12mg/L (20-50 micromol/L)
15
Q
Monitoring for carbamazepine
A
FBC, renal function, LFT
16
Q
Warning signs for carbamazepine?
A
- toxicity - incoordination, blurred vision. diplopia. drowsiness, nystagmus, ataxia, arrhythmias, n+v. diarrhoea, hyponatramia
- blood disorders e.g. leucopenia, thrombocytopenia (fever, sore throat, unexplained bruising or bleeding)
- skin disorders e.g. toxic epidermal necrolysis (mouth ulcers, rash)
- hepatic disorders e.g. hepatitis
- antiepileptic hypersensitivity syndrome - symptoms commonly seen are fever, rash, swollen lymph nodes
17
Q
What is the major route of elimination for carbamazepine?
A
- hepatic metabolism
18
Q
Action required for when carbamazepine warning signs are present?
A
- advise patient to report immediately to a doctor if any warning signs occur
- ensure patient recieves same brand of medicine each time
- ensure patient is aware of law regarding seizures and driving
- inform patinent of potential interations and they should check with pharm/doc before any new meds/OTCs
19
Q
Carbamazepine interactions?
A
- Increased plasma conc with acetazolamide, cimeditine, clarithromycin, erythromycin, fluoxetine, isoniazid
- decreased plasma conc with phenytoin, rifabutin, st johns wort
- carbamazepine reduces plasma conc of antipsychotics, corticosteroids, coumarins, eplerenone, oestrogens, progestogens, simvastatin
- anticonvuslant effect antagonised by mefloquine, antipsychotics
- possible increased risk of convulsions when antiepileptics given with orlistat
20
Q
What is systemic chemotherapy?
A
Oral, IV, SC, IM with aim of maximal therapeutic cytotoxic effect whilst avoiding extreme toxicity to normal healthy issues
21
Q
What is regional chemotherapy?
A
Intrathecal, intraarterial which is aimed at delivering cytotoxics directly into cavity in which tumour is located or blood vessel supplying tumour therefore minimising side effects
22
Q
Common side effects of chemo?
A
- Extravasation of IV drugs: leakage of cytotoxic drug from vein into subcutaneuos or subdermal tissue, which can lead to permanent tissue damage; refer to local guidlines for prevention and prompt managment
- N+V: can cause distress and may lead to refusal of treatment so prophylaxis of n+v is very important; drugs have varying emetogenic potential
- Bone marrow supression: (except vincristine and bleomycin) commonly occurs 7-10 days after administration, important to treat infection before or when starting cytotoxic, neutropenic sepsis is a medical emergency
- Other: oral mucositis, diarrhoea, fatugue, organ toxicities (e.g, neurotoxicity with vinca alkaloids so IV administration only, cardiotoxicity with anthracyclines), hyperericaemia, urothelial toxicity
23
Q
Warning signs of neutropenic sepsis (from chemo)?
A
- feeling unwell and/or have temperature
- develop shivering episodes/flu like symptoms
- uncontrolled gum/nose bleeds or unusual bruising
- diarrhoea and/or uncontrolled vomiting
- develop mouth ulcers that stop patient eating/drinking
24
Q
Action required for neutropenic sepsis?
A
- A&E immediately withot taking paracetamol or seeking advice (to avoid dangerous delay in start antibiotics)
- advise patient to report side effects to dr immediately
- for a drug that causes moderate-severe emesis, antiemetics should always be prescribed on a regular basis
- advise patient to maintain good oral hygeine (rinsing mouth more frequently and effective brushing of teeth with soft brush 2-3 times daily) to avoid mucositis
25
What is the therapeutic range for ciclosporins?
depends on clinical situation and indication for treatment. Loading doses may be required
26
Monitoring for ciclosporin?
- FBC, LFT, serum K and Mg, blood lipids, renal function (including creatinine, urea), BP, dermatological and physical examination
27
Warning signs for ciclosporin?
- neurotoxicity e.g. tremor, headache, encephalopathy (e.g. confusion, convulsions)
- blood disorders (signs of infection fever etc) e.g. leucopenia, thrombocytopenia
- liver toxicity e.g. jaundice, n+v, abdominal discomfort, dark urine
- nephrotoxicity e.g. elevated serum creatinine concentrations
- other signs of toxicity - vomiting, drowsiness, tachycardia
- hypertension
- headache
- gingival hyperplasia
28
Action required when warning signs of ciclosporin present ?
- advise patient to report immediately to a doctor if any warning signs occur
- hypertension is a common side effect of ciclosporin therapy. Advise patient to have their blood pressure monitored regularly
- warn patients they must not recieve immunisation with live vaccines
- brand-specific prescribing is recommended (if changing brand monitor closely for changes in ciclosporin level, serum creatinine and BP)
- avoid excessive UV light exposure - use wide spec spf (may reduce risk of secondary skin malignancies). Patients with atopic dermatitis and psoriasis should avoid use of UVB or PUVA
- advise patient to avoid high potassium diet and grapefruit juice. the oral solution formulations can be taken with orange or apple juices to improve taste
29
Ciclosporin interactions?
- increased plasma conc with clarithromycin, diltiazem, erythromycin, fluconazole, grapefruit juice, itraconazole, ketoconazole, miconazole, metoclopramide, verapamil, colchicine (with which concomitant use also increases risk of nephrotoxicity and myotoxocity) and tacrolimus (AVOID)
- decreased plasma conc with carbamazepine, orlistat, phenobarbital, phenytoin, rifampicin, st johns wort
- increased risk of hyperkalaemia when given with ACE inhibitors or ARBs, aldosterone antagonists
- increased risk of nephrotoxicity when give with NSAIDs and increased plasna conc of diclofenac
- increased risk of myopathy when given with atorvastatin, fluvastatin, pravastatin, rosuvastatin, simvastatin (avoid concomitant use)
30
Monitoring for corticosteroids?
- BP
- blood lipids
- serum K
- body weight and height in children and adolescents
- bone mineral density
- blood glucose
- eye exam (for intraocular pressure, cataracts)
- signs of adrenal suppression
31
Corticosteroid warning signs
- paradoxical bronchospasm (constriction of the airways)
- symptoms of uncontrolled asthma e.g cough, wheeze, tight chest
- frequent courses of antibiotics and/or oral corticosteroids
- adrenal suppression e,g. nausea, vomiting, weight loss, fatigue, headache, muscular weakness
- immunosuppression, e.g. chicken pox, measles, oral candidiasis, more serious infections e.g. TB, septicaemia, oculat fungal or viral infections
- psychiatric reactions e.g suicidal thoughts, nightmares, depression, insomnia
32
Action required when corticosteroid warning signs present ?
- report immediatly to doctor
- give patient steroid treatment card if long term. explain that they must not stop treatment abruptly after prolonged treatment (>3weeks)
- check patient is taking oral steroids in the morning as a single dose
- ensure patients rinse their mouth/clean teeth after using inhaled ccsteroids
- if the patient has not already had chicken pox/measles, advise them to avoid anyone with these infections
33
Corticosteroid interactions?
- metabolism of ccsteroids accelerated by carbamazepine, phenobarbital and rifamycins
- ccs may induce or enhance anticoagulant effect of coumarins
- high dosse ccs can impaire immune response to vaccines; avoid concomittant use with live vaccines
- ccs can mask GI effects of NSAIDS (incl aspirin); avoid concomitant use if possible and consider gastroprotection
- hypokalaemia can be severe when given with other drugs that lower serum K e.g loop and thiazide diuretics
- effects if antihypertensive and oral hypoglycaemic drugs are antagonised by glucocorticoids
34
what is the therapeutic range of digoxin?
1-2mcg/L. Loading dose may be required
35
Monitoring for digoxin?
- serum electrolytes (K, Mg, Ca) as electrolyte imbalance (hypokalaemia, hypomagnesaemia, hypocalcaemia) can potentiate toxicity, renal function, heart rate (maintained at greater than 60bpm)
36
Major route of elimination for digoxin?
Renal excretion; hepatic metabolism to active metabolites
37
Warning signs for digoxin?
- cardiac e.g. arrhythmias. heart block
- neurological e.g. weakness, lethargy, dizziness, headache, mental confusion, psychosis
- GI e.g. anorexia, nausea, vomiting, diarhoea, abdominal pain
- visual e.g. blurred and/or yellow vision
38
Action required when digoxin warning signs present?
- advise patient to report immediately to a doctor
* dosage forms have different bioavailabilities (change of dose required to maintain same plasma-digoxin conc). Please refer to manufacturer spc for more info
- IV: 100%
- tablet: 50-90%
- elixir: 75%
39
Digoxin interactions?
- - increased plasma conc with alprazolamamiodarone, ciclosporin. diltiazem, itraconazole, lercanidipine, macrolides, mirabegron, nicardipine, nifedipine, quinine, sprionolactone and verapamil
- reduced plasma conc with st johns wort
- concomitant administration of acetazolamide, amphotericin, loop diuretics or thiazides and related diuretics can cause hypokalaemia that increases the risk of cardiac toxicity and digoxin toxicity
- drugs that impair renal function can affect the plasma digoxing conc e.g. NSAIDs. ACE inhibs
40
Diuretics monitoring?
- BP
- serum electrolytes (Na+, K)
- weight (as a measure of fluid loss)
41
Warning signs for diurtetics?
- heaviness in the centre of the chest
- water retention
- depression
- extreme tiredness. thirst or excessive urination
- irregular heartbeat, muscle weakness, nausea
- gout
42
Action required when diuretics warning signs present ?
- report to dr stat
- advise patient to sit up and stand slowly first thing in the morn to prevent postural hypotension and report to gp if hypotensive symptoms persist
- if dizziness experienced, advise patient to avoid drinking or operating machinery
- drink adequate amount of fluids each day
- interactions
43
Digoxin interactions?
- Enhanced hypotensive effect with ACE inhib, alpha blockers, ARBs
- increased risk of severe hyperkalaemia when potassium-sparing diuretics or aldosterone antagonists given with ACE, ARBs, ciclosporin, potassium salts, tacrolimus
- hypokalaemia caused by acetazolamide, loop diuretics, thiazides or thiazide-related diuretics increases risk of ventricular arrhythmias with amisulpride, atomoxetine, pimozide, sotalol
- hypokalaemia caused by diuretics increases the risk of cardiac toxicity with cardiac toxicity with cardiac glycosides
- plasma conc of eplerenone increased by clarithromycin (AVOID), itraconazole
- plasma conc of eplererone reduced by carbamazepine, phenobarbital, phenytoin, rifampicin (AVOID), st johns wort
- increased risk of ototoxicity when loop diuretics given with aminoglycosides (gentamycin etc), polymixins, vancomycin
44
Gentamycin therapeutic range?
For multiple daily dose regimes, one hour (peak) serum concentration should be 5-10mg/L (3-5mg/L for endocartitis), pre-dose (trough) conc should be <2mg/L (<1mg/L for endocarditis); for once daily dose regimens consult local guidelines.
Loading doses may be required
45
Major route of elimination for gentamycin?
Renal excretion
46
Gentamycin monitoring?
- renal function (nephrotoxicitt)
- auditory and vestibular function (ototoxicity which is irreversible)
- serum-aminoglycoside conc must be determined in the elderly, those with renal impairment, if high doses given, obesity and in cyctic fibrosis
47
Gentamycin warning signs?
hearing impairment or hearing disturbance --> report to doctor if this occurs
*other action: ensure patient is hydrated and drinking adequate amounts of fluid to prevent dehydration before starting treatment
48
Gentamycin interactions?
- increased risk of nephrotoxicity when aminoglycosides such as gentamycin are given with ciclosporin, tacrolimus, vancomycin
- increased risk of ototoxicity when aminoglycosides gievn with loop diuretics, vancomycin
49
Insulin monitoring?
- blood glucose
| - HbA1c
50
Warning signs for insulin?
- recurring episodes of hypoglycaemia e.g. sweating, palpitations, confusion, drowsiness
- signs of diabetic ketoacidosis e.g. nausea, vomiting, drowsiness
- any symptoms of liver toxicity, heart failure or pancreatitis e.g. jaundice, abdominal pain, vomiting, fluid in abdomen, fatigue, breathless, swollen ankles
- ulceration of foot tissue
51
Action required when insulin warning signs present ?
- report to dr stat
- check patient has insulin passport and have notified DVLA
- check theyre aware of safe disposal of needles and never to re use
- check pt has an annual diabetic review with rxer
- check injection technique
- check blood glucose monitoring methods and understanding
- check prescriptions for insulin state the dose in units not abbrev
- check insulin is administered with the correct insulin syringe or pen device and correct size of needle. IV syringes must never be used for insulin administration
52
Insulin interactions?
- substances that may ENHANCE blood glucose lowering activity (reduce insulin requirements) and increase risk of hypoglycaemia include oral antidiabetics, ACE inhibs, MAOIs, salicylates, sulphonamide antibiotics
- substances that may REDUCE blood gluc lowering activity (increase insulin requirements) include corticosteroids, diuretics, sympathomimetics (e.g. epinephrine, salbutamol, terbutaline), thyroid hormones, oral contraceptives (oestrogens, progestogens)
- betablockers or alcohol may potentiate and/or weaken the blood glucose lowering activity of insulin
53
Danger of IV medicines and infusion fluid ?
- wherever possible IV meds should be infused separately. Physical and chemical incompatibilites may occur with loss of potency, increase in toxicity or other adverse effects. All medicine mixtures should be checked for signs of incompatibility, which can include cloudiness, change in colour, precipitation or haze.
54
Important IV drug to be careful administering example?
- potassim chloride
- potassium overdose can be fatal. ready-mixed solutions contatining K should be used where possible. KCl 20% w/v concentrate for solution for infusion must not be injected undiluted. It must be diluted with NaCl IV infusion 0.9% w/v or other suitable diluent to a conc not more than 40mmol per litre, mixed well and given by slow IV infusion, under ECG control, ensuring adequate urine flow and with careful monitoring of electrolytes.
- rapid infusion can be toxic to the heart and cardiac arrythmias may occur. manufacturer recommendation is that the infusion rate should not exceed 20mmol K per hour. A higher conc and higher infusion rate may be given in severe potassium depletion under specialist supervision
55
Lithium therapeutic range?
0.4 - 1mmol/L (lower end for maintenance therapy and elderly patients) and 0.8-1mmol/L for acute episodes of mania and for patients who have previously relapsed or have sub-syndromal symptoms
56
Lithium monitoring?
- serum lithim concentration
- renal function
- cardiac function
- thyroid function
57
Major route of elimination for lithium?
renal; freely filtered at glomerulus with 80% reabsorbed
58
Warning signs for lithium?
- increasing GI disturbances e.g. vomiting, diarrhoea
- visual disturbances e.g blurred vision
- CNS disturbances e.g. drowsiness, unsteadiness, confusion
- fine tremor increasing to coarse tremor, muscle weakness
- incontinence, polyuria (excessive urination)
- serum conc over 2mmol/L (severe overdosage) - seizures, coma, renal failure, arrhythmias, BP changes, circulatory failrue, sudden death
- signs and symptoms of hypothyroidism (e.g. unexplained fatigue)
- signs and symptoms of renal dysfunction (e.g. polyuria and polysipsia)
- signs and symptoms of benign intracranial hypertension (e.g. persistent headache and visual disturbance
59
Action required for lithium warning signs?
- report to dr stat
- check patient knows important of staying on same brand of lithium and has a lithium treatment pack
- inform patient to keep a constant adequate salt and water intake (especially if they have an infection or during hot spells)
- advise patient on OTC interactions and to avoid alcohol
- counsel patient on risks on driving if they feel sleepy
- stress importance of not stopping lithium suddenly unless told by dr
60
Lithium interactions?
- increased risk of toxicity with ACE inhibs, ARBs, loop diuretics, thiazides and related diuretics, NSAIDs, K-sparing diuretics, aldosterone antagonists, metronidazole, SSRIs (and CNS effects), tricyclics
- increased risk of ventricular arrhythmias with amiodarone
- risk of neurotoxicity with methyldopa, pheytoin, carbamazepine, diltiazem, verapamil
- increased risk of extrapyramidal side effects with clozapine, haloperidol, sulpiride, phenothiazines, risperidone, flupentixol, zuclopenthixol
61
Methotrexate monitoring?
- FBC
- renal function
- liver function
* local protocols for frequency of monitoring may vary
62
Warning signs for methotrexate?
- GI toxicity e.g stomatitis
- liver toxicity e.g. jaundice, nausea, vomiting, abdominal discomfort, dark urine
- blood disorders - bone marrow suppression e.g. sore throat, bruising, mouth ulcers, fever, rash
- pulomary toxicity - pneumonitis e.g. dysponea, cough
- pregnancy and breastfeeing
63
Action required for methotrexate warning signs?
- report to dr stat
- ensure patients are aware methotrexate tablets are to be taken once a week, on the same day each week, to take folic acid as prescribed and the patient is given a methotrexate treatment booklet
- counsel pt on importance of effective contraception during treatment
- advise pt to avoid OTC preps containing NSAIDs/aspirin
- recommend to pt to obtain annual flu vaccine but live vaccines should be avoided
64
Methotrexate interactions?
- increased plasma conc and risk of hepatotoxicity with acitretin (avoid)
- excretion reduced by NSAIDs and penicillins therefore increased risk of toxocitiy. Also increased risk of toxicity when given with ciprofolxacin, doxycycline, tetracycline, sufonamides, ciclosporin, PPIs, leflunomide
- increased risk of haemotological toxicity when given with sulfamethoxazole (co-trimoxazole) or trimethoprim
65
NSAIDs monitoring?
- BP (especially after dose changes)
- renal function
- liver function
- haemoglobin in those with risk factors for GI bleeding
66
NSAIDS warning signs?
- black stools of 'coffee ground' vomit, suggesting chronic GI bleeding
- iron deficiency anaemia, suggesting chronic GI bleeding (fatigue, dizziness, pale skin, SOB)
- progressive unintentional weight loss or difficulty swallowing
- pregnancy and breastfeeding
- swollen ankles or feet
- unexplained, persistent recent-onset dyspepsia
- worsening of asthma
67
Action required for NSAID warning signs?
- report to dr stat
- check NSAID rxd is suitable for pt; accounting for GI and CVS risk, high dose or regular dose, appropriate duration of treatment
- take lowest effective dose for shortest period of time to control symptoms. Longterm treatment to be reviewed periodically
- all patients of any age rxed NSAIDs for osteoarthritis or RA or pt over 45 who are rxed NSAIDs for lower back pain should be co-prescribed gastroprotection e.g. PPI
- recommend that oral NSAID is taken with or just after food
- inform patient of potential interactions, the need to check with a pharmacist or doctor before taking any new medications (especially OTC NSAIDs)
68
NSAID interactions?
- possible increased risk of convulsions when given with quinolones
- possible enhanced anticoagulant effect of coumarins (warfarin) and phenindione
- possible enhanced effects of sulfonylureas
- increased risk of bleeding with dabigatran, heparins, SSRIs, venlafexine, antiplatelets
- increased risk of nephrotoxicity when given with ciclosporin, tacrolimus, diuretics (also antagonism of diuretic effect)
- may reduce excretion of lithium or methotrexate (increasing risk of toxicity)
- increased side effects with concomitant use of other NSAIDs, aspirin
- NSAIDs antagonise hypotensive effect of BBs, CCBs, ACEis, ARBs, ABs, nitrates
69
Opiates monitoring?
- pain
| - sedation
70
Opiates warning signs?
- respiratory depression (difficulty breathing)
- bradycardia, hypotension e.g. faint/dizzy
- extreme sleepiness
- reduced conc or confusion e.g. not able to think, walk or talk normally
- cyanosis (of lips, ears, nose)
- vivid dreams. hallucinations or nightmares
- convulsions
- pinpoint pupils
- dependence and tolerance
71
Opiate dependence and tolerance behaviours?
```
Psycoholgical dependence or addiction behaviours:
- craving
- compulsive use
- continued use despite harm
Physical dependence or withdrawal occurs when drug is stopped suddenly or when dose is tapered rapidly and signs include
- sweating
- restlessness
- tremor
- increase in usual pain
- diarrhoea
- vomiting and anxiety
Tolerance can develop during long term treatment where increasing doses are required to achieve the same therapeutic effect
```
72
Action required for opiate warning signs?
- rport to dr
- advise pt to avoid driving and other at risk activities if experiencing drowsiness especially during first few days of initial treatment, when dose is changed, or if they feel unfit to drive
- ensure that a dose increase should be no more than 50% of previous dose
- advise to not stop treatmnet suddenly
73
Opiates interactions?
- enhanced hypotensive and sedative effects when given with alcohol
- tramadol enhances anticoagulant effect of warfarin
- decreased effect of fentanyl, morphine, codeine, methadone, and alfentanil when given with rifampicin
- possible CNS excitation or depression (hypertension or hypotension) when opiates given with MAOIs
74
Oral antiplatelets monitoring?
- renal function
| - liver function
75
Oral antiplatalet warning signs ?
- chronic GI bleeding e.g. severe abdominal pain, vomiting blood, tarry black or blood mixed with stools, feeling out of breath and dizziness
- heaviness in the centre of the chest
- severe itching or rash
- unusual brusing or bleeding
- preg and breastfeeding
76
Action required for oral antiplatelet warning signs?
- report to dr
- inform patients on MR dipyridamole capsules to discard them 6 weeks after opening the original container
- ensure tablets/capsules are taken with or just after food (excpet dipyridamole, which should be taken 30-60 mins before food)
- check patient is taking clopidogrel for correct duration of treatment according to indication
77
Oral antiplatelet interactions?
- clopidogrel antiplatelet effect possibly reduced by carbamazepine, cimetidine, ciprofloxacin, erythromycin, fluconazole, fluoxetine, itraconazole, oxcarbazepine, moclobemide, lansoprazole, pantoprazole, rabeprazole, etravirine
- clopidogrel antiplatelet effect reduced by omeprazole, esomeprazole
- clopidogrel enhances anticoagulant effect of warfarin anf phenindione; manufacturer advises avoif with warfarin
- clopidogrel increases plasma conc of rosuvastatin
- dipyridamole enhances effects of adenosine (increased risk of toxicity), warfarin and phenindione, heparin
- an increased risk of bleeding wiht concomitant use of other antiplatelet drugs, NSAIDs, SSRIs, methotrexate, anticoagulants
78
Phenytoin therapeutic range?
10-20mg/L (or 40-80micromol/L)
- non linear relationship between dose and plasma drug concentration: small changes in dose/ missed dose/change in drug absorption can result in marked changed in plasma drug concentration
79
Phenytoin monitoring?
- serum conc
- ECG and BP with IV use
- liver function
- FBC
- serum folate
- vitamin D
- Phenytoin is highly protein bound; patients with impaired liver function, elderly or those who are gravely ill may show early signs of toxicity
80
Major route of elimination for phenytoin?
hepatic metabolism
81
Phenytoin warning signs?
- toxicity e.g. nystagmus, ataxia, slurred speach, hyperglycaemia, diplopia or blurred vision, confusion
- skin disorders e.g. rash, toxic epidermal necrolysis
- blood disorders (fever, sore throat, mouth ulcers, unexplained bruising or bleeding) e.g. leucopenia, aplastic anaemia, megaloblastic anaemia
- suicidal thoughts
- low vitamin D levels e.g. rickets, osteomalacia
82
Action required for phenytoin warning signs?
- report dr
- use caution when dispensing: brand-specific rxing recommended as preparations containing phenytoin sodium (100mg) are equivalent to those containing phenytoin base (92mg). The dose is the same for all phenytoin products when initiating therapy, but if switching between formulations, the difference in phenytoin content may be clinically significant
83
Phenytoin interactions?
- increased plasma conc with amiodarone, chloramphenicol, cimetidine, disulfiram, diltiazem, fluconazole, fluoxetine, miconazole, topiramate, trimethoprim (also increased antifolate effect), metronidazole, clarithromycin, telithromycin (avoid during and 2 weeks after phenytoin)
- reduced plasma concentrations with rifamycins, st johns wort, theophylline, itraconazole, ciclosporin
- phenytoin accelerates metabolism of coumarins (warfarin) (possibitiy of reduced anticoagulant effect by enhancement also reported), corticosteroids, oestrogens, progestogens
- anticonvulsant effect possibly antagonised by antipsychotics, mefloquine, SSRIs, tricyclics, and tricylcic-related antidepressants
- phenytoin possibly reduces plasma concentration of aripiprazole, itraconazole, oestrogens and progestogens (reduced contraceptive effect), theophylline and tricyclics
84
Tacrolimus monitoring?
- BP
- ECG (for cardiomyopathy)
- fasting blood glucose conc
- renal function
- liver function
- serum electrolytes (particularly K)
- haemotological, neurological (including visual) and coagulation parameters
- whole blood-tacrolimus trough conc should be monitored especially during episodes of diarrhoea
85
Tacrolimus warning signs?
- neurotoxicity e,g, tremor, headache
- nephrotoxicity e.g. elevated serum creatinine concentrations
- eye disorders e.g. blurred vision, photophobia
- skin disorders e.g. rash, toxic epidermal necrolysis
- blood disorders (signs of infection such as fever, sore throat, mouth ulcers, also unexplained bruising or bleeding) e,g leucopenia, thrombocytopenia
- hyperglycaemia - diabetes e.g. increased thirst or excessive urination
- CV disorders - cardiomyopathy, arhythmias, hypertension e.g. irregular heartbeat, heaviness in the centre of the chest triggered by effort or emotion
- liver toxicity e.g. jaundice, nausea, vomiting, abdominal discomfort, dark urine
86
Action required for tacrolimus warning signs ?
- report to dr
- advise pt to avoid excessive UV/sun exposure and use wide spec spf (may reduce risk of secondary skin malignancies)
- oral tacrolimus medicines should be rxed and dispensed by brand name only to minimise switching between products to reduce risk of toxicity and graft rejection.
- ensure patient understands the importance of taking immunosuppressants regularly
- advise pt that tacrolimus may affect performace of skilled tasks (e.g. driving) and to avoid undertaking them if they feel unfit
- warn patients recieving tacrolimus that they must not recieve immunisation with live vaccines
- advise pt to avoid a high potassium diet and grapefruit juice
87
Tacrolimus interactions?
- increased plasma concentrations with clarithromycin, diltiazem, erythromycin, fluconazole, grapefruit juice, itraconazole, nifedipine, omeprazole, ranolazine
- reduced plasma concentration with phenobarbital, st johns wort, rifampicin, phenytoin
- increased risk of nephrotoxicity when given with aminoglycosides, amphotericin and NSAIDs (especially ibuprofen), certain antivirals (e.g aciclovir, ganciclovir)
- tacrolimus increases plasma conc of ciclosporin
- increased risk of hyperkalaemia when given with k-sparing diuretics (e.g. amiloride, spironolactone), potasssium salts, ARBs
88
Theophylline (aminophylline) therapeutic range?
- 10-20mg/L (55-110micromol/L) although a plasma theophylline conc of 5-15mg/L may still be effective). Loading doses may be required
89
Theophylline monitoring?
- serum potassium
| - plasma theophylline conc
90
Theophylline elimination route?
Major hepatic metabolism
91
Theophylline warning signs ?
- toxicity e.g. vomiting (may be intractable), agitation, restlessness, dilated pupils, sinus tachycardia, hyperglycaemia, severe hypokalaemia may develop rapidly, haematemesis, convulsions, cardiac rhythms
- symptoms of uncontrolled asthma (cough, wheeze, tight chest)
- frequent courses of antibiotics and/or oral corticosteroids
92
Action required for theopylline warning signs?
- report to dr
- inform pt of potential interactions with theophylline and the need to double check before taking new meds
- advise to inform GP before stopping or starting smoking - as smoking increasing clearance so higher doses needed
- emphasise the importance of maintaining on the same brand ; rate of absorption from MR preparations can vary between brand
93
Theophylline interactions?
- potentially serious hypokalaemia may result frim beta 2 agonist therapy. Caution required in severe asthma, because this effect may be potentiated by concomitant use of theophylline, corticosteroids and diuretics as well as hypoxia. Plasma potassium should be monitored in severe asthma
- increased plasma concentrations with diltiazem, cimetidine, ciprofloxacin, erythromycin, oestrogens, fluvoxamine, verapamil
- possible increased risk of convulsions when theophylline given with quinolines
- reduced plasma concentrations with carbamazepine, primidone, phenobarbital and phenytoin, ritonavir
94
Vancomycin therapeutic range?
- trough 10-15mg/L (15-20mg/L for endocarditis or less sensitive strains of methicillin-resistant staphylococcus or compliacted infections caused by s.aureus)
loading doses may be required
95
Vancomycin major route of elimination?
- renal; 70-90% excreted unchanged in urine
96
Vancomycin monitoring?
- serum K
- FBC
- renal function
- auditory function in elderly
- urinalysis
97
Vancomycin warning signs?
- hearing loss, vertigo, dizziness, tinnitus
- flushing of the upper body (red man syndrome)
- blood disorders (signs of infection such as fever, sore throat, mouth ulcers, also unexplained brusing or bleeding) e.g neutropenia, thrombocytopenia
- Phlebitis (irritant to tissue)
- nephrotoxocity e.g. elevated serum creatinine concs
- skin disorders e.g. rashes, toxic epidermal necrolysis, pruritus
*other: hypotension and anaphylactic reactions can occur if administered too quickly
98
Action required for vancomycin warning signs?
report to dr immeadiately
99
Vancomycin interactions?
- increased risk of nephrotoxicity and ototoxicity when vancomycin given with ciclosporin, aminoglycosides, polymixin antifungals
- increased risk of ototoxicity when vancomycin given with loop diuretics
- vancomycin enhances effects of suxamethonium
100
Warfarin therapeutic range?
Assessed according to INR every 3 months (more frequent if changes in clinical status e.g. acute illness, diarrheoa and vomiting, medication changes, signs of bleeding/thrombosis, non-adherence, recent high/low INR, dramatic change in diet); target value depends on clinical situation and indication for treatment
101
Warfarin monitoring?
- clotting screen
- liver function
- renal function
- FBC
- BP
- thyroid function
102
Warfarin warning signs?
- signs of excessive bleeding e.g. nosebleeds, bleeding from wounds
- signs of thrombosis e.g. pain, swelling, tenderness usually in calf, redness of skin, chest pain, SOB
- rash, skin necrosis, purple toes
- headaches, confusion
- diarrhoea and vomiting (may lead to poor absorption)
103
Action required for warfarin warning signs?
- report to dr
- ensure warfarin is taken at the same time of day, once a day with a full glass of water and that the patient is aware that if a dose is missed they should not double the dose the next day
- check pt has an oral anticoagulant pack with their record booklet and alert card and ensure that they have a system for recording INR and doses
- advise the pt to notify their anticoagulation clinic of any changes to medication, lifestyle or diet.
- check patient is familiar with strengths and colours of warfarin tabs
- ensure warfarin dose is expressed in mg and not the number of tablets
104
Warfarin interactions?
- anticoagulant effect enhanced by amiodarone, anabolic steroids, azithromycin, cephalosporins, cimetidine, clarithromycin, clopidogrel, high dose corticosteroids, cranberry juice, dipyridamole, disolfiram, entacapone, erythromycin, esomeprazole, fibrates, fluconazole, fluvastatin, glucosamine, itraconazole. methylphenidate, metronidazole, miconazole (including topical fomulations)
DAKTARIN), nalidixic acid, norfloxacin, NSAIDs, ofloxacin, omeprazole, propafenone, rosuvastatin, SSRIs, st johns wort, sulfonamides, tamoxifen, testosterone, tetracyclines, thyroid hormones, tramadol, tricyclics, venlafaxine and vitamin E
- anticoagulant effect reduced by acitretin, azathioprine, carbamazepine, clopidogrel, griseofulvin, mercaptopurine, phenobarbital, phenytoin, rifamycins, sucralfate, vitamin K
- anticoagulant effect may be enhanced and/or reduced by corticosteroids and colestyramine
105
What drugs have a narrow therapeutic index?
- gentamycin
- warfarin
- lithium
- digoxin
- theophylline
- methotrexate
- phenytoin
- insulin
- ciclosporin
